WO2022169911A1 - Matériau collagène stratifié et son procédé de production - Google Patents

Matériau collagène stratifié et son procédé de production Download PDF

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Publication number
WO2022169911A1
WO2022169911A1 PCT/US2022/014995 US2022014995W WO2022169911A1 WO 2022169911 A1 WO2022169911 A1 WO 2022169911A1 US 2022014995 W US2022014995 W US 2022014995W WO 2022169911 A1 WO2022169911 A1 WO 2022169911A1
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WIPO (PCT)
Prior art keywords
collagen
laminated
contiguous layers
compressed
woven
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PCT/US2022/014995
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English (en)
Inventor
Steven Palmer Ford
Alain L. FORGET
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Datascope Corp.
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Publication of WO2022169911A1 publication Critical patent/WO2022169911A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10—Polypeptides; Proteins
    • A61L24/102—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/01—Non-adhesive bandages or dressings
    • A61F13/01008—Non-adhesive bandages or dressings characterised by the material
    • A61F13/01012—Non-adhesive bandages or dressings characterised by the material being made of natural material, e.g. cellulose-, protein-, collagen-based
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0036—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0042—Materials resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10—Polypeptides; Proteins
    • A61L24/104—Gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/04—Materials for stopping bleeding

Definitions

  • the field of the present disclosure pertains to laminated collagen materials and processes for their production. More specifically, the present disclosure pertains to laminated collagen materials having blood absorbing and hemostatic properties.
  • Collagen is the main structural protein found in the connective tissues of the body. Medically, collagen is used to promote tissue growth, for reconstruction of bone and tissue, for wound healing, and for other surgical and reconstructive purposes.
  • US Patent 6,977,231 describes a suturable adhesion-preventing membrane composed of at least one non-woven fabric layer made of collagen fibers, or a laminated membranous substance consisting of at least one non-woven fabric layer made of collagen fibers and at least one sponge layer made of collagen, and a coating layer of gelatin or hyaluronic acid on the surface or surfaces of the membrane.
  • the membrane described therein may be sutured, is biocompatible, has an adhesion-preventing effect, and promotes tissue regeneration.
  • US Patent 7,084,082 describes a collagen material having physical properties that allow suturing.
  • the collagen material is characterized by filling or having inside a substance having biocompatibility that can be degraded and absorbed in the body into a matrix of a non-woven fabric-like multi-element structure of collagen fibers having ultra-fine fibers of collagen as its basic unit.
  • the collagen material may be used in a medical material such as an artificial tube for nerve, an artificial tube for spinal cord, an artificial esophagus, an artificial trachea, an artificial blood vessel, an artificial valve or alternative medical membranes such as an artificial endocranium, artificial ligamenta, artificial tendons, surgical sutures, surgical prostheses, surgical reinforcement, wound protecting materials, artificial skin and an artificial cornea.
  • a medical material such as an artificial tube for nerve, an artificial tube for spinal cord, an artificial esophagus, an artificial trachea, an artificial blood vessel, an artificial valve or alternative medical membranes such as an artificial endocranium, artificial ligamenta, artificial tendons, surgical sutures, surgical prostheses, surgical reinforcement, wound protecting materials, artificial skin and an artificial cornea.
  • US Patent 9,162,006 describes a hemostatic porous sponge comprising a matrix of a fibrous biomaterial (such as collagen, a protein, a biopolymer, or a polysaccharide) and particles of a fluid absorbing, particulate material adhered to the matrix material.
  • a fibrous biomaterial such as collagen, a protein, a biopolymer, or a polysaccharide
  • the sponge described therein has hemostatic properties.
  • a laminated collagen material comprising: a first set of one or more nonwoven contiguous layers of compressed fibrillar collagen filaments, wherein the fibrillar collagen filaments comprise bundles of compressed collagen fibers; a sheet of a compressed gelatin sponge, wherein the gelatin sponge comprises a matrix of gelatin and spaces within the matrix of gelatin; and a first transition zone formed between the one or more non-woven contiguous layers and the sheet, wherein within the first transition zone, some bundles of the compressed collagen fibers protrude into the compressed gelatin sponge so as to substantially fill those spaces within the matrix of gelatin at the first transition zone.
  • Clause 2 The laminated collagen material of clause 1, wherein the one or more nonwoven contiguous layers of compressed fibrillar collagen filaments comprise two layers.
  • Clause 3 The laminated collagen material of clause 1, wherein the one or more nonwoven contiguous layers of compressed fibrillar collagen filaments comprise three layers.
  • Clause 4 The laminated collagen material of clause 1, wherein the one or more nonwoven contiguous layers of compressed fibrillar collagen filaments comprise four layers.
  • Clause 5 The laminated collagen material of any one of the preceding clauses, wherein the mean diameter of the compressed collagen fibers is from about 0.5 pm to about 10.0 pm.
  • Clause 6 The laminated collagen material of any one of the preceding clauses, wherein the thickness of the first set of one or more non-woven contiguous layers is from about 150 pm to about 250 pm, and the thickness of the sheet is from about 350 pm to about 400 pm.
  • Clause 7 The laminated collagen material of any one of the preceding clauses, wherein the density of the laminated collagen material is about 155.8 g/cm 3 .
  • Clause 8 The laminated collagen material of any one of the preceding clauses, further comprising: a second set of one or more non-woven contiguous layers of compressed fibrillar collagen filaments, wherein the fibrillar collagen filaments comprise bundles of compressed collagen fibers, and wherein the second set of one or more non-woven contiguous layers is disposed on the opposite side of the sheet than the first set of one or more non-woven contiguous layers; and a second transition zone formed between the second set of one or more non-woven contiguous layers and the sheet, wherein within the second transition zone, some bundles of compressed collagen fibers from the second set of one or more non-woven contiguous layers protrude into the compressed gelatin sponge so as to substantially fill those spaces within the matrix of gelatin at the second transition zone.
  • Clause 9 The laminated collagen material of clause 8, wherein the second set of one or more non-woven contiguous layers of compressed fibrillar collagen filaments comprises two layers.
  • Clause 10 The laminated collagen material of clause 8, wherein the second set of one or more non-woven contiguous layers of compressed fibrillar collagen filaments comprises three layers.
  • Clause 11 The laminated collagen material of clause 8, wherein the second set of one or more non-woven contiguous layers of compressed fibrillar collagen filaments comprises four layers.
  • Clause 12 The laminated collagen material of any one of clauses 8-11, wherein the mean diameter of the compressed collagen fibers of the first and second sets is from about 0.4 pm to about 8.0 pm.
  • Clause 13 The laminated collagen material of any one of clauses 8-12, wherein the thickness of the first set of one or more non-woven contiguous layers is from about 70 pm to about 100 pm, the thickness of the second set of one or more non-woven contiguous layers is from about 70 pm to about 100 pm, and the thickness of the sheet is from about 150 pm to about 200 pm.
  • Clause 14 The laminated collagen material of any one of the preceding clauses, wherein the fibrillar collagen filaments of the first set and the second set comprise residual amounts of sodium chloride.
  • Clause 15 The laminated collagen material of any one of the preceding clauses, wherein the fibrillar collagen filaments of the first set and the second set are salt-cured fibrillary collagen filaments.
  • Clause 16 The laminated collagen material of any one of the preceding clauses, wherein the one or more non-woven contiguous layers of the first set are layered along the same axis.
  • Clause 17 The laminated collagen material of any one of the preceding clauses, wherein the one or more non-woven contiguous layers of the second set are layered along the same axis.
  • Clause 18 The laminated collagen material of any one of clauses 1-15 or 17, wherein the one or more non-woven contiguous layers of the first set are layered along one or more axes.
  • Clause 19 The laminated collagen material of any one of clauses 1-16 or 18, wherein the one or more non-woven contiguous layers of the second set are layered along one or more axes.
  • Clause 20 The laminated collagen material of any one of the preceding clauses, wherein the laminated collagen material is porous so as to absorb blood and promote hemostasis when in contact with blood.
  • Clause 21 The laminated collagen material of any one of clauses 8-20, wherein the density of the laminated collagen material is about 196.7 g/cm 3 .
  • Clause 22 The laminated collagen material of any one of the preceding clauses, wherein the mean length of the compressed fibrillar collagen filaments of the first set or the second set is from about 20 mm to about 150 mm.
  • Clause 23 The laminated collagen material of any one of the preceding clauses, wherein the mean length of the compressed collagen fibers of the first set or the second set is from about 5 mm to about 15 mm.
  • a process for producing a laminated collagen material comprising the following steps: providing a first set of one or more non-woven contiguous layers of fibrillar collagen filaments, wherein the fibrillar collagen filaments comprise bundles of collagen fibers, wherein mean diameter of the bundles is from about 20 pm to about 300 pm, and mean diameter of the collagen fibers is from about 100 nm to about 300 nm; providing a sheet of a gelatin sponge adjacent to the first set of one or more non-woven contiguous layers, wherein the gelatin sponge comprises a matrix of gelatin and spaces within the matrix of gelatin; and compressing the first set of one or more non-woven contiguous layers and the sheet together to form a first transition zone between the one or more non-woven contiguous layers and the sheet of the laminated collagen material; wherein within the first transition zone formed by compression, some bundles of compressed collagen fibers protrude into the compressed gelatin sponge so as to substantially fill those spaces within the matrix of gelatin at the first transition zone.
  • Clause 25 The process of clause 24, further comprising: prior to compressing the first set of one or more non-woven contiguous layers and the sheet together, providing a second set of one or more non-woven contiguous layers of fibrillar collagen filaments, wherein the fibrillar collagen filaments comprise bundles of collagen fibers, wherein the mean diameter of the bundles in the second set is from about 20 pm to about 300 pm, the mean diameter of the collagen fibers in the second set is from about 100 nm to about 300 nm, and wherein the second set of one or more non-woven contiguous layers is disposed on the opposite side of the sheet than the first set of one or more non-woven contiguous layers; and when compressing the first set of one or more non-woven contiguous layers and the sheet, also compressing the second set of one or more non-woven contiguous layers together with the sheet to form the laminated collagen material; wherein the laminated collagen material further includes a second transition zone formed between the second set of one or more non-woven contiguous layers and
  • Clause 26 The process of clause 24 or 25, wherein the mean length of the fibrillar collagen filaments of the first set or the second set is from about 20 mm to about 150 mm.
  • Clause 27 The process of any one of clauses 24, 25 or 26, wherein the mean length of the collagen fibers of the first set or the second set is from about 5 mm to about 15 mm.
  • Clause 28 A laminated collagen material produced by the process of any one of clauses 24-27.
  • Figure 1A shows components used to produce a laminated collagen material in accordance with a non-limiting illustrative inventive embodiment of the present disclosure.
  • Figure IB shows components used to produce a laminated collagen material in accordance with another non-limiting illustrative inventive embodiment of the present disclosure.
  • Figure 2 shows a laminated collagen material in accordance with a non-limiting illustrative inventive embodiment of the present disclosure.
  • Figure 3 shows a laminated collagen material in accordance with another non-limiting illustrative inventive embodiment of the present disclosure.
  • Figure 4 shows a scanning electron microscope (SEM) image (at 50x magnification) of a non-woven layer of fibrillar collagen filaments.
  • Figure 5 shows an SEM image (at 10,000x magnification) of a non-woven layer of fibrillar collagen filaments.
  • Figure 6 shows an SEM image (at 50x magnification) of a cross-section of two nonwoven layers of fibrillar collagen filaments.
  • Figure 7 shows an SEM image (at 200x magnification) of a cross-section of a nonwoven layer of fibrillar collagen filaments.
  • Figure 8 shows an SEM image (at 20x magnification) of a laminated collagen material in accordance with a non-limiting illustrative inventive embodiment of the present disclosure.
  • Figure 9 shows an SEM image (at l,000x magnification) of the laminated collagen material shown in Figure 8.
  • Figure 10 shows an SEM image (at 20x magnification) of the laminated collagen material shown in Figure 8.
  • Figure 11 shows an SEM image (at l,000x magnification) of the laminated collagen material shown in Figure 8.
  • Figure 12 shows an SEM image (at lOOx magnification) of a cross-section of the laminated collagen material shown in Figure 8.
  • Figure 13 shows an SEM image (at 500x magnification) of a cross-section of the laminated collagen material shown in Figure 8.
  • Figure 14 shows an SEM image (at 20x magnification) of a laminated collagen material in accordance with another non-limiting illustrative inventive embodiment of the present disclosure.
  • Figure 15 shows an SEM image (at 10,000x magnification) of the laminated collagen material shown in Figure 14.
  • Figure 16 shows an SEM image (at 20x magnification) of the laminated collagen material shown in Figure 14.
  • Figure 17 shows an SEM image (at l,000x magnification) of the laminated collagen material shown in Figure 14.
  • Figure 18 shows an SEM image (at 500x magnification) of a cross-section of the laminated collagen material shown in Figure 14.
  • Figure 19 shows an SEM image (at lOOx magnification) of a cross-section of the laminated collagen material shown in Figure 14.
  • Figure 20 shows a stress-strain curve for the laminated collagen material shown in Figure 2 and the laminated collagen material shown in Figure 3.
  • any type of collagen fibers can compose the bundles used to produce the laminated collagen material of the present disclosure.
  • the collagen fibers are not lyophilized, thereby leading to less denaturing of the collagen, and longer collagen fibers.
  • An example of a preferred process for producing the collagen fibers includes using bovine tendons as the collagen source, washing the tendons, treating them with sodium hydroxide, treating them with hydrochloric acid, compressing the tendons, treating them with sodium chloride, and dehydrating via acetone treatment.
  • This preferred process of producing the collagen fibers is described in detail in US Patent No. 4,404,033, which is incorporated herein by reference in its entirety.
  • Collagen fibers produced by this preferred process may include residual amounts of sodium chloride.
  • collagen fibers produced by this preferred process may be salt-cured collagen fibers.
  • the collagen fibers are then processed by conventional textile equipment into a nonwoven layer of fibrillar collagen filaments, wherein the fibrillar collagen filaments comprise bundles of the collagen fibers.
  • collagen fibers can be processed by a carding machine with layering attachments to produce one or more non-woven layers of fibrillar collagen filaments.
  • the one or more non-woven contiguous layers of fibrillar collagen filaments are layered along the same axis.
  • the non-woven contiguous layers of fibrillar collagen filaments are layered along more than one axis.
  • the fibrillar collagen filaments may include residual amounts of sodium chloride.
  • the fibrillar collagen filaments may be salt-cured fibrillar collagen filaments.
  • Figure 1A shows the components used to produce an embodiment of the laminated collagen material of the present disclosure.
  • Figure 1A there is a set (1) of two non-woven contiguous layers of fibrillar collagen filaments, and on top of these two non-woven contiguous layers are two individual sheets (2) of a gelatin sponge.
  • the two sheets (2) shown are identical and are used to produce two samples of an embodiment of the laminated collagen material of the present disclosure.
  • the set (1) in Figure 1A consists of two non-woven contiguous
  • the set (1) may contain one or more non-woven contiguous layers of fibrillar collagen filaments as a component in producing an embodiment of the laminated collagen material of the present disclosure.
  • a set (1) of one, three or four non-woven contiguous layer(s) of fibrillar collagen filaments are used to produce an embodiment of the laminated collagen material of the present disclosure.
  • the fibrillar collagen filaments comprise bundles of collagen fibers.
  • Figure 4 shows an SEM image (at 50x magnification) of a non-woven layer of fibrillar collagen filaments. As seen in Figure 4, via visual inspection of the SEM image, there are bundles of collagen fibers having diameters, for example, of 27.4 pm and 207.8 pm. Nonlimiting examples of the bundles of collagen fibers of the present disclosure include those having a mean diameter in the range of about 20 pm to about 300 pm.
  • Figure 5 shows an SEM image (at 10,000x magnification) of a non-woven layer of fibrillar collagen filaments.
  • individual collagen fibers which make up the bundles
  • diameters for example, of 96 nm, 158 nm and 169 nm.
  • Non-limiting examples of the individual collagen fibers (which make up the bundles) of the present disclosure include those having a mean diameter in the range of about 100 nm to about 300 nm.
  • Figure 6 at 50x magnification
  • Figure 7 at 200x magnification
  • Figure 6 and 7 show SEM images of a cross-section of two non-woven layers of fibrillar collagen filaments and one non-woven layer of fibrillar collagen filaments, respectively.
  • the structural characteristics of the non-woven layer of fibrillar collagen filaments in its crosssection is similar to the structural characteristics of the non-woven layer of fibrillar collagen filaments on its surface (as shown in Figures 4 and 5).
  • the gelatin sponge comprises a matrix of gelatin and spaces within the matrix of gelatin.
  • the gelatin sponge comprises lyophilized hydrolyzed collagen.
  • Non-limiting examples of the gelatin sponge include the Surgispon® sponge sold by Aegis Lifesciences. Additional types of gelatins and additional types of sponges may be used as the sheet (2) in some embodiments of the present disclosure.
  • Figure IB shows the components used to produce another embodiment of the laminated collagen material of the present disclosure.
  • FIG IB there is a second set (3) of two nonwoven contiguous layers of fibrillar collagen filaments, and this second set (3) is placed on top of a sheet (2) of a gelatin sponge (not shown), which is placed on top of a first set (1) of two nonwoven contiguous layers of fibrillar collagen filaments (not shown).
  • the sheet (2) and the first set (1) of two non-woven contiguous layers are not shown in Figure IB because they are covered up by the second set (3) of two non-woven contiguous layers.
  • the sheet (2) of a gelatin sponge is sandwiched between the first set (1) of two non-woven contiguous layers (on the bottom) and the second set (3) of two non-woven contiguous layers (on the top).
  • the second set (3) in Figure IB consists of two nonwoven contiguous layers of fibrillar collagen filaments
  • the second set (3) may alternatively contain one or more non-woven contiguous layers of fibrillar collagen filaments as a component in producing an embodiment of the laminated collagen material of the present disclosure.
  • a second set (3) of one, three or four non-woven contiguous layer(s) of fibrillar collagen filaments is used to produce an embodiment of the laminated collagen material of the present disclosure.
  • the laminated collagen material is sufficiently porous so as to absorb blood and promote hemostasis when in contact with blood.
  • the set (1) of two non-woven contiguous layers of fibrillar collagen filaments is positioned on paper (6), and a sheet (2) of the gelatin sponge is placed on top of and adjacent to the set (1) of two non-woven contiguous layers of fibrillar collagen filaments.
  • the set (1) of two non-woven contiguous layers and a sheet (2) are compressed together to form an embodiment of the laminated collagen material.
  • the compression may be done via any type of compression machine, such as a calender machine (i.e., a compression roller).
  • the set (1) of two non-woven contiguous layers and the adjacent sheet (2) were fed through the rollers of a 2-Bowl Ramisch Kleinewefers Calender (type: RKK 210 P), with the pressure set to 15 kN using the pressure regulator.
  • the embodiment of the laminated collagen material (4) as formed by this process is shown in Figure 2.
  • the density of the laminated collagen material (4) shown in Figure 2 is about 155.8 g/cm 3 after compression by this calendar machine.
  • the external surface of the compressed gelatin sponge layer (2) of the laminated collagen material (4) is pocked with regular pitlike depressions resulting from the fact that the pressing surface of the calendar machine has regular protrusions that help prevent the material (4) from slipping out of the calendar machine during compression.
  • Figures 8 and 9 show SEM images (at 20x magnification and l,000x magnification, respectively) of the embodiment of the laminated collagen material (4) shown in Figure 2, viewing the side of the set (1) of two non-woven contiguous layers of fibrillar collagen filaments.
  • there are compressed collagen fibers having diameters, for example, of 633 nm, 1.1 pm, 1.8 pm, 3.0 pm and 9.4 pm.
  • Nonlimiting examples of the compressed collagen fibers include those having a mean diameter in the range of about 0.5 pm to about 10.0 pm.
  • Figures 10 and 11 show SEM images (at 20x magnification and l,000x magnification, respectively) of the embodiment of the laminated collagen material (4) shown in Figure 2, viewing the side of the sheet (2) of the gelatin sponge.
  • the gelatin sponge comprises a matrix of gelatin (110) and spaces (111) within the matrix of gelatin.
  • Figures 12 and 13 show SEM images (at lOOx magnification and 500x magnification, respectively) of a cross-section of the embodiment of the laminated collagen material (4) shown in Figure 2.
  • Figure 13 shows the first transition zone (130) formed by compression, wherein some bundles of compressed collagen fibers (131) protrude into the compressed gelatin sponge (132) so as to substantially fill those spaces within the matrix of gelatin (133) at the first transition zone.
  • the thickness of the set (121) of two non-woven contiguous layers of compressed fibrillar collagen filaments is about 199.4 pm
  • the thickness of the sheet (132) of the compressed gelatin sponge is about 374.5 pm.
  • Non-limiting examples of the set of one or more non-woven contiguous layers of compressed fibrillar collagen filaments include those having a thickness in the range of about 150 pm to about 250 pm, and non-limiting examples of the sheet of a compressed gelatin sponge include those having a thickness in the range of about 350 pm to about 400 pm.
  • Non-limiting examples of the laminated collagen material include those having a total thickness in the range of about 400 pm to about 1,000 pm, about 500 pm to about 1,000 pm, or about 500 pm to about 650 pm.
  • the second set (3) of two non-woven contiguous layers of fibrillar collagen filaments are placed on top of a sheet (2) of the gelatin sponge (not easily seen through the second set (3) of two non-woven contiguous layers of fibrillar collagen filaments), which is placed on top of a first set (1) of two non-woven contiguous layers of fibrillar collagen filaments (not viewable because it is covered by both the sheet (2) and the second set (3) of two non-woven contiguous layers of fibrillar collagen filaments).
  • the sheet (2) of a gelatin sponge is sandwiched between the first set (1) of two non-woven contiguous layers (on the bottom) and the second set (3) of two non-woven contiguous layers (on the top).
  • the first set (1) of two non-woven contiguous layers, the sheet (2) and the second set (3) of two non-woven contiguous layers are compressed together (with the sheet (2) sandwiched between the first set (1) of two non-woven contiguous layers and the second set (3) of two non-woven contiguous layers) to form an embodiment of the laminated collagen material.
  • the compression may be done via any type of compression machine, such as a calender machine (i.e., a compression roller).
  • the first set (1) of two non-woven contiguous layers, the sheet (2) and the second set (3) of two non-woven contiguous layers were fed through the rollers of a 2-Bowl Ramisch Kleinewefers Calender (type: RKK 210 P), with the pressure set to 15 kN using the pressure regulator.
  • the embodiment of the laminated collagen material (5) as formed by this process is shown in Figure 3.
  • the density of the laminated collagen material (5) shown in Figure 3 is about 196.7 g/cm 3 after compression by this calendar machine.
  • the external surface of the compressed gelatin sponge layer (2) of the laminated collagen material (5) is pocked with regular pitlike depressions resulting from the fact that the pressing surface of the calendar machine has regular protrusions that help prevent the material (5) from slipping out of the calendar machine during compression.
  • Figures 14 and 15 show SEM images (at 20x magnification and 10,000x magnification, respectively) of the embodiment of the laminated collagen material (5) shown in Figure 3, viewing the side of the first set (1) of two non-woven contiguous layers of compressed fibrillar collagen filaments.
  • the compressed collagen fibers include those having a mean diameter in the range of about 50 nm to about 600 nm, about 50 nm to about 8.0 pm, or about 0.4 pm to about 8.0 pm.
  • Figures 16 and 17 show SEM images (at 20x magnification and l,000x magnification, respectively) of the embodiment of the laminated collagen material (5) shown in Figure 3, viewing the side of the second set (3) of two non-woven contiguous layers of compressed fibrillar collagen filaments.
  • compressed collagen fibers having diameters, for example, of 422 nm, 955 nm, 2.0 pm and 6.6 pm.
  • Non-limiting examples of the compressed collagen fibers include those having a mean diameter in the range of about 0.4 pm to about 8.0 pm.
  • first transition zone between the first set (1) of two non-woven contiguous layers and the sheet (2), and a second transition zone between the second set (3) of two non-woven contiguous layers and the sheet (2).
  • first transition zone formed by compression some bundles of compressed collagen fibers from the first set of two non-woven contiguous layers protrude into the compressed gelatin sponge so as to substantially fill those spaces within the matrix of gelatin at the first transition zone.
  • second transition zone formed by compression some bundles of compressed collagen fibers from the second set of two non-woven contiguous layers protrude into the compressed gelatin sponge so as to substantially fill those spaces within the matrix of gelatin at the second transition zone.
  • Figures 18 and 19 show SEM images (at 500x magnification and lOOx magnification, respectively) of a cross-section of the embodiment of the laminated collagen material (5) shown in Figure 3.
  • Figure 18 shows the second transition zone (180) formed by compression, wherein some bundles of compressed collagen fibers (181) protrude into the compressed gelatin sponge (182) so as to substantially fill those spaces within the matrix of gelatin (183) at the second transition zone.
  • the thickness of the first set (191) of two non-woven contiguous layers of compressed fibrillar collagen filaments is about 70 pm to about 100 pm
  • the thickness of the sheet (182) of the compressed gelatin sponge is about 150 pm to about 200 pm
  • the thickness of the second set (192) of two nonwoven contiguous layers of compressed fibrillar collagen filaments is about 70 pm to about 100 pm.
  • the laminated collagen material include those having a total thickness in the range of about 290 pm to about 1,000 pm, about 290 pm to about 400 pm, or about 400 pm to about 1,000 pm.
  • Figure 20 shows a stress-strain diagram obtained by dynamic mechanical analysis (DMA), with a controlled force test method.
  • DMA testing was done in accordance with ASTM D7028, using a Q800 DMA from TA Instruments.
  • the vertical axis corresponds to stress (MPa)
  • the horizontal axis corresponds to strain (%).
  • the two curves 201 denote two samples from the laminated collagen material (4) shown in Figure 2 and produced in Example 1A
  • the two curves 202 denote two samples from the laminated collagen material (5) shown in Figure 3 and produced in Example IB.
  • the laminated collagen material (5) shown in Figure 3 and produced in Example IB is substantially stronger and more elastic than the laminated collagen material (4) shown in Figure 2 and produced in Example 1A.
  • the laminated collagen materials (5) shown in Figure 3 and produced in Example IB exhibit up to about 5% to about 5.75% deformation before breaking
  • the laminated collagen materials (4) shown in Figure 2 and produced in Example 1A exhibit up to about 3.25% deformation before breaking.
  • the addition of the second set of two non-woven contiguous layers of compressed fibrillar collagen filaments in Example IB serves to substantially increase strength and elasticity of the resulting laminated collagen material.
  • the sheet of the compressed gelatin sponge provides resistance to any applied stress and makes the laminated collagen materials (4) and (5) more elastic and stronger as compared to non-woven contiguous layer(s) of compressed fibrillar collagen filaments by themselves, which are inelastic and easily breakable.
  • compressed fibrillar collagen filaments absorb blood and become wet, eventually turning into a gel that cannot hold sutures. This limits their usage and application as a hemostatic material.
  • the laminated collagen materials of the present disclosure provide the advantage of being more elastic and stronger than compressed fibrillar collagen filaments alone.
  • the laminated collagen materials of the present disclosure provide a clinical benefit over the usage of compressed fibrillar collagen filaments alone.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Surgery (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Dispersion Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Materials For Medical Uses (AREA)
  • Laminated Bodies (AREA)
  • Prostheses (AREA)

Abstract

L'invention concerne un matériau collagène stratifié comprenant un premier ensemble d'une ou plusieurs couches contiguës de non-tissé de filaments de collagène fibrillaires comprimés, une feuille d'éponge de gélatine comprimée, et une première zone de transition formée entre la ou les couches contiguës de non-tissé et la feuille. Les filaments de collagène fibrillaires comprennent des faisceaux de fibres de collagène comprimées, et l'éponge de gélatine comprend une matrice de gélatine et des espaces à l'intérieur de la matrice de gélatine. Dans la première zone de transition, certains faisceaux de fibres de collagène comprimées font saillie dans l'éponge de gélatine comprimée de manière à remplir sensiblement ces espaces dans la matrice de gélatine à la première zone de transition. Un procédé de production d'un matériau collagène stratifié consiste à produire un premier ensemble d'une ou plusieurs couches contiguës de non-tissé de filaments de collagène fibrillaires, à produire une feuille d'éponge de gélatine adjacente au premier ensemble d'une ou plusieurs couches contiguës de non-tissé, et à comprimer ensemble le premier ensemble d'une ou plusieurs couches contiguës de non-tissé et la feuille pour former une première zone de transition entre la ou les couches contiguës de non-tissé et la feuille du matériau collagène stratifié.
PCT/US2022/014995 2021-02-03 2022-02-02 Matériau collagène stratifié et son procédé de production WO2022169911A1 (fr)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060041320A1 (en) * 1999-01-21 2006-02-23 Kazuhisa Matsuda Suturable adhesion-preventing membrane
US20080260801A1 (en) * 2005-11-17 2008-10-23 Gelita Ag Composite material, especially for medical use, and method for producing the material
US20110070288A1 (en) * 2009-09-22 2011-03-24 Sasa Andjelic Composite layered hemostasis device
US20120077272A1 (en) * 2006-10-23 2012-03-29 Alexander Kharazi Cellular scaffold
US20140308325A1 (en) * 2010-04-07 2014-10-16 Baxter International Inc. Hemostatic sponge
US20150132360A1 (en) * 2013-11-08 2015-05-14 Warsaw Orthopedic, Inc. Multi-layered anti-adhesion device

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060041320A1 (en) * 1999-01-21 2006-02-23 Kazuhisa Matsuda Suturable adhesion-preventing membrane
US20080260801A1 (en) * 2005-11-17 2008-10-23 Gelita Ag Composite material, especially for medical use, and method for producing the material
US20120077272A1 (en) * 2006-10-23 2012-03-29 Alexander Kharazi Cellular scaffold
US20110070288A1 (en) * 2009-09-22 2011-03-24 Sasa Andjelic Composite layered hemostasis device
US20140308325A1 (en) * 2010-04-07 2014-10-16 Baxter International Inc. Hemostatic sponge
US20150132360A1 (en) * 2013-11-08 2015-05-14 Warsaw Orthopedic, Inc. Multi-layered anti-adhesion device

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